Daniel Sand

Expression of microRNAs in basal cell carcinoma

Background  Perturbations in the expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers. Differentially expressed miRNAs have not been systematically evaluated in basal cell carcinoma (BCC) of the skin.

MicroRNAs and the skin: Tiny players in the body's largest organ

MicroRNAs (miRNAs) are very small endogenous RNA molecules about 22-25 nucleotides in length, capable of post-transcriptional gene regulation. miRNAs bind to their target messenger RNAs (mRNAs), leading to cleavage or suppression of target mRNA translation based on the degree of complementarity. miRNAs have recently been shown to play pivotal roles in diverse developmental and cellular processes and linked to a variety of skin diseases and cancers. Disruption of miRNA metabolism is also involved in wound healing and inflammatory skin conditions. Here, we review the role of miRNAs in cutaneous biology.

Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi

Perturbations in microRNA (miRNA) expression profiles have been reported for cutaneous malignant melanoma (CMM) predominantly when examined in cell lines. Despite the rapidly growing number of newly discovered human miRNA sequences, the availability of up-to-date miRNA expression profiles for clinical samples of primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM), and benign melanocytic nevi (BMN) is limited. Specimens excised from the center of tumors (lesional) from patients with PCMM (n=9), CMMM (n=4), or BMN (n=8) were obtained during surgery. An exploratory microarray analysis was performed by miRNA expression profiling based on Agilent platform screening for 1205 human miRNAs. The results from the microarray analysis were validated by TaqMan quantitative real-time polymerase chain reaction. In addition to several miRNAs previously known to be associated with CMM, 19 unidentified miRNA candidates were found to be dysregulated in CMM patient samples. Among the 19 novel miRNA candidates, the genes hsa-miR-22, hsa-miR-130b, hsa-miR-146b-5p, hsa-miR-223, hsa-miR-301a, hsa-miR-484, hsa-miR-663, hsa-miR-720, hsa-miR-1260, hsa-miR-1274a, hsa-miR-1274b, hsa-miR-3663-3p, hsa-miR-4281, and hsa-miR-4286 were upregulated, and the genes hsa-miR-24-1*, hsa-miR-26a, hsa-miR-4291, hsa-miR-4317, and hsa-miR-4324 were downregulated. The results of this study partially confirm previous CMM miRNA profiling studies identifying miRNAs that are dysregulated in CMM. However, we report several novel miRNA candidates in CMM tumors; these miRNA sequences require further validation and functional analysis to evaluate whether they play a role in the pathogenesis of CMM.

Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components argonaute-1, argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer.

The microprocessor complex mediates intranuclear biogenesis of precursor microRNAs from the primary microRNA transcript. Extranuclear, mature microRNAs are incorporated into the RNA‐induced silencing complex (RISC) before interaction with complementary target mRNA leads to transcriptional repression or cleavage. In this study, we investigated the expression profiles of the microprocessor complex subunit DiGeorge syndrome critical region gene 8 (DGCR8) and the RISC components argonaute‐1 (AGO1), argonaute‐2 (AGO2), as well as double‐stranded RNA‐binding proteins PACT, TARBP1, and TARBP2 in epithelial skin cancer and its premalignant stage. Patients with premalignant actinic keratoses (AK, n = 6), basal cell carcinomas (BCC, n = 15), and squamous cell carcinomas (SCC, n = 7) were included in the study. Punch biopsies were harvested from the center of the tumors (lesional), from healthy skin sites (intraindividual controls), and from healthy skin sites in a healthy control group (n = 16; interindividual control). The DGCR8, AGO1, AGO2, PACT, TARBP1, and TARBP2 mRNA expression levels were detected by quantitative real‐time reverse transcriptase polymerase chain reaction. The DGCR8, AGO1, AGO2, PACT, and TARBP1 expression levels were significantly higher in the AK, BCC, and SCC groups than the healthy controls (P < 0.05). There was no significant difference in the TARBP2 expression levels between groups (P > 0.05). This study indicates that major components of the miRNA pathway, such as the microprocessor complex and RISC, are dysregulated in epithelial skin cancer.

Microarray analysis of microRNA expression in cutaneous squamous cell carcinoma

BACKGROUND MicroRNAs (miRNAs) are a novel class of short RNAs that are capable epigenetically regulating gene expression in eukaryotes. MicroRNAs have been shown to be dysregulated in a variety of cancers. The data on miRNA expression in cutaneous squamous cell carcinoma (cSCC) are very limited, and microarray-based miRNA expression profiles of cSCC have not yet been determined. OBJECTIVE To describe differentially expressed miRNAs in cSCC. METHODS Seven patients with cSCC were enrolled in the present study. Tumor biopsies (n=7) were taken from the center of each tumor. Adjacent healthy skin (n=7) was biopsied as a control (intraindividual control). miRNA expression profiles of all specimens were detected by microarray miRNA expression profiling based on miRBAse 16 scanning for 1205 potential human miRNA target sequences. The microarray results were confirmed by TaqMan quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS Non-stringent filtering with a non-adjusted p ≤ 0.05 revealed thirteen up-regulated and eighteen down-regulated miRNAs. Non-stringent filtering with a non-adjusted p ≤ 0.01 revealed three up-regulated (hsa-miR-135b, hsa-miR-424 and hsa-miR-766) and six down-regulated (hsa-miR-30a*, hsa-miR-378, hsa-miR-145, hsa-miR-140-3p, hsa-miR-30a and hsa-miR-26a) miRNAs in cSCC. CONCLUSION This study reveals differentially expressed miRNAs that may play a role in the molecular pathogenesis of cSCC and that are excellent candidates for further validation and functional analysis.

Surgical and medical emergencies on board European aircraft: a retrospective study of 10189 cases

IntroductionIn-flight medical and surgical emergencies (IMEs) onboard commercial aircrafts occur quite commonly. However, little epidemiological research exists concerning these incidents.MethodsThirty-two European airlines were asked to provide anonymous data on medical flight reports of IMEs for the years 2002 to 2007. The total number of incidents was correlated to revenue passenger kilometers (rpk). Additionally, on-board births and deaths, flight diversions, flight routes (continental/intercontinental) and involvement of a physician or medical professional in providing therapy were analysed.ResultsOnly four airlines, of which two participated in this study, were able to provide the necessary data. A total of 10,189 cases of IMEs were analysed. Syncope was the most common medical condition reported (5307 cases, 53.5%) followed by gastrointestinal disorders (926 cases, 8.9%) and cardiac conditions (509 cases, 4.9%). The most common surgical conditions were thrombosis (47 cases, 0.5%) and appendicitis (27 cases, 0.25%). In 2.8% of all IMEs, an aircraft diversion was performed. In 86% of cases, a physician or medical professional was involved in providing therapy. A mean (standard deviation) of 14 (+/- 2.3, 10.8 to 16.6 interquartile range) IMEs per billion rpk was calculated.ConclusionsThe study demonstrates that although aviation is regulated by a variety of national and international laws, standardised documentation of IMEs is inadequate and needs further development.

Diagnostic value of hyperbilirubinemia as a predictive factor for appendiceal perforation in acute appendicitis

BACKGROUND Appendiceal perforation in patients with acute appendicitis may cause a variety of potentially life-threatening complications. Escherichia coli endotoxin has been shown to impact physiological bile flow in vivo. This had led to the theory that hyperbilirubinemia in patients with appendicitis may have a predictive potential for the preoperative diagnosis of appendiceal perforation. The aim of this retrospective study was to investigate the diagnostic value of hyperbilirubinemia as a preoperative laboratory marker for appendiceal perforation in patients with acute appendicitis. METHODS We identified 538 patients (306 female; 232 male, mean age, 35.6 y) with histologically proved acute appendicitis who underwent laparoscopic or conventional appendectomy between January 2004 and December 2007 in a surgical department of an academic teaching hospital. A retrospective multiple chart review of the medical records including laboratory values and histologic results was conducted. RESULTS The mean bilirubin level of all patients was .9 mg/dL (+/-.6 SD mg/dL; range, .1-4.3 mg/dL; median, .7 mg/dL). Patients with appendiceal perforation, however, had a mean bilirubin level of 1.5 mg/dL (+/-.9 SD mg/dL; range, .4-4.3 mg/dL; median, 1.4 mg/dL), which was significantly higher than those with a nonperforated appendicitis (P < .05). The specificity of hyperbilirubinemia for appendiceal perforation was .86 compared with .55 for white blood count and .35 for C-reactive protein. Sensitivity was .7 compared with .81 for white blood count and .96 for C-reactive protein. CONCLUSIONS Patients with hyperbilirubinemia and clinical symptoms of appendicitis should be identified as having a higher probability of appendiceal perforation than those with normal bilirubin levels.

Surgical treatment of axillary hyperhidrosis: a study comparing liposuction cannulas with a suction-curettage cannula.

Background:Suction-curettage is a minimally invasive surgical approach for the treatment of focal axillary hyperhidrosis. Studies comparing the efficacy of different surgical cannulas are missing. Therefore, we gravimetrically compared a specially designed cannula versus 2 standard liposuction cannulas. Methods:Axillary suction-curettage was performed in 42 patients (n = 42). Fourteen patients (n = 14) were operated with a 1-hole liposuction cannula, 14 patients (n = 14) with a larger 3-hole liposuction cannula, and 14 (n = 14) with a sharp suction-curettage cannula. Sweat rates in mg/min were measured by gravimetry before and 6 months after surgery. Results:Sweat rate in the 1-hole liposuction cannula group was significantly reduced from 57.65 ± 5.85 mg/min to 32.58 ± 4.64 mg/min (P < 0.001), corresponding to a reduction of 44.15%. Patients operated with the larger 3-hole liposuction cannula showed a significant reduction of sweat rate from 63.95 ± 8.25 mg/min to 33.14 ± 6.25 mg/min (P < 0.001), corresponding to a reduction of 49.19%. The largest reduction of sweat rates (63.07%) was achieved with the suction-curettage cannula (61.85 ± 9.03 mg/min to 21.27 ± 4.42 mg/min (P < 0.001). No severe side effects were observed. Conclusion:Due to the higher efficacy we recommend performing suction-curettage with a sharp suction-curettage cannula.

Fat tissue after lipolysis of lipomas: A histopathological and immunohistochemical study

Background:  Injections with Lipostabil®, a phosphatidylcholine (PDC) containing substance, have become a popular technique to treat localized fat accumulation and lipomas for aesthetic reasons. Despite its frequent use, the mechanism of action of PDC and histological changes of treated fat tissue still remain unclear. To investigate the histological changes of lipomas after treatment with PDC.

A Randomized, Controlled, Double-Blind Study Evaluating Melanin-Encapsulated Liposomes as a Chromophore for Laser Hair Removal of Blond, White, and Gray Hair

Introduction:Laser hair removal of blond and white hair is a complicated task with often unsatisfactory results as a result of a lack of laser-absorbing chromophore. In the present study, we investigated if repetitive external application of liposomal melanin (Lipoxome; Dalton Medicare B.V., Zevenbergschen Hoek, The Netherlands) enables removal of blond/white and gray hair with a diode laser. Methods:Forty-two areas of blond, gray, or white facial and body hair of 16 patients were treated with a liposomal melanin spray (Lipoxome) and 3 cycles of 800 nm diode laser at intervals of 8 weeks (28–40 J/cm2). A control group of 16 patients applied physiological saline spray before diode laser treatment. Hair regrowth was measured 8 weeks after each cycle and additionally 6 months after the last treatment by counting the number of terminal hairs compared with baseline pretreatment values. Complications and treatment outcomes were documented. Results:Mean regrowth in the liposomal melanin group was 83% after 3 treatment cycles. Six months after therapy, average terminal hair count compared with baseline pretreatment showed 14% reduction. Although significant difference was seen compared with the control group showing a 10% reduction of hair growth after 6 months (P < 0.05), the clinical outcome was disappointing. Conclusions:Melanin-encapsulated liposomal spray in combination with diode laser treatment showed significant higher efficacy in the treatment of white and blond hair compared with a control group. However, the clinically observed hair reduction was so weak that additional effort as well as higher costs argues against the application of the tested formulation.